title: Tyramine antagonistic properties of AGN 1135, an irreversible inhibitor of monoamine oxidase type B.
abstract: 1 The effects of the irreversible monoamine oxidase (MAO) inhibitors, AGN 1133, AGN 1135 and (-)-deprenyl, on tyramine and noradrenaline responses and uptake of [3H]-metaraminol were investigated in the isolated vas deferens of the rat. Uptake of [3H]-metaraminol and [3H]-octopamine was compared in mouse vas deferens. The modification of tyramine and noradrenaline-induced pressor responses by AGN 1133 and AGN 1135 was examined in anaesthetized rats and cats. 2 AGN 1133 (7.5 x 10(-6)M) greatly potentiated responses to tyramine in the rat isolated vas deferens. Both AGN 1135 and (-)-deprenyl inhibited tyramine responses selectively at concentrations above 10(-5)M (which caused almost complete inhibition of MAO types A and B) but tyramine responses were potentiated on washing out the inhibitors. 3 AGN 1135 (10(-4)M) and (-)-deprenyl (10-5)M) inhibited [3H]-metaraminol uptake by about 20% in rat and mouse vas deferens; neither inhibitor affected [3H]-octopamine uptake in mouse vas deferens. Desmethylimipramine (10(-6)M) inhibited amine uptake by more than 70%. 4 AGN 1133 (1.5 mg/kg) potentiated pressor responses to tyramine in rats and cats whereas AGN 1135 (1.5 mg/kg) did not. 5 AGN 1135 possesses tyramine antagonistic activity which is qualitatively similar to that of (-)-deprenyl but which cannot satisfactorily be explained by inhibition of neuronal or granula amine uptake.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D008680:Metaraminol / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D009655:Octopamine; D051381:Rats; D012642:Selegiline / Q000494:pharmacology; D014439:Tyramine / Q000037:antagonists & inhibitors*; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D007189:Indans; D007192:Indenes; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D009655:Octopamine; D012642:Selegiline; D008680:Metaraminol; D003010:Clorgyline; D014439:Tyramine